This invention relates generally to systems and methods for mixing and dispensing microbubble pharmaceuticals.
Ultrasound-mediated destruction of microbubbles carrying drugs has been found to be useful as a noninvasive drug delivery system. Drugs or other therapeutic agents can be incorporated into the microbubbles in a number of different ways, including binding of the drug to the microbubble shell and attachment of site-specific ligands. For example, perfluorocarbon-filled microbubbles are sufficiently stable for circulating in the vasculature as blood pool agents; they act as carriers of these agents until the site of interest is reached. Ultrasound applied over the skin surface can then be used to burst the microbubbles at this site, causing localized release of the drug at specific site locations. Albumin-encapsulated microbubbles have also been used and delivered to a specific organ target by site-directed acoustic ultrasound.
Typically when the microbubble delivery of an active pharmaceutical ingredient (API) is either an approved drug or during FDA clinical approval, the drug will be mixed with microbubbles just prior to the bolus being given to the patient. When hand mixing these two components there may be variables that cannot be controlled between various locations where the mixing occurs, or between operators. Other parameters, relating to mixing, including pressure and temperature, microbubble stability, and storage may also vary. These parameters are difficult to control manually, thus a method of reducing variability and parameter control is needed to optimize dosage and efficacy of the drug. Furthermore mechanical mixing of the microbubbles with the API must be carefully controlled. Excessive shear or turbulence may also cause rupture of the microbubbles.
Another limitation of current methodology and devices used for preparation and microbubble delivery is that, as with other pharmaceutical samples there is a requirement for maintaining sterility. For pharmaceutical products, sterility assurance is essential and there can be no risk of contamination to the product. Current methods and devices require the sample to be handled and exposed to the environment and current pressure regulating devices often use inlet and exit ports to control pressure by the introduction or removal of gas streams. As such, any pressure control device in contact with the sample will have to be sterilized and sterility will have to be assured during the preparation and delivery of the sample. A system to control pressure in a closed environment is desirable.
Thus, a need therefore exists for microbubble preparation and delivery device that can reduce variability, avoid rupture, and control various parameters. It is also desirable that the device maintains sterility during preparation and drug delivery using a closed system to control pressure.